Five years of support are requested to create a faculty development program that will enable junior faculty involved in research at the three Ph.D. granting institutions in Kansas (KU at Lawrence and the KU School of Medicine in Kansas City, and Kansas State University) to become more competitive for securing NIH grant support and to recruit senior faculty who could develop new research programs. A strong mentoring program comprised of Dr. Narayan and individual Project mentors, all of whom are established investigators, a writing program designed to assist COBRE members in preparation of manuscripts and grants, and an external advisory committee who will review progress of all Projects twice annually will be established. Five Cores, one administrative, one focused on writing, and three technical, have already been established in the final year of the present COBRE to expedite the new research program. The COBRE has received extensive new institutional support in the form of FTEs and new research equipment in the three technical Cores. The research theme is centered on basic and translational mechanisms aimed at inhibiting replication of pathogenic microbes. Studies will be focused on identification of microbial genes and gene products that have a seminal role in their replication and use of these as targets for therapy. The translational portion of the COBRE will be dedicated to use of gene therapy using nanoparticles as vectors for delivery in vivo. The COBRE support will be used to support three-year Projects of four junior faculty and one senior faculty, funds for enhancement of recruitment packages of new faculty at the three institutions, and funds for further recruitment of senior faculty who could contribute to development of new research programs. Funds will also be used to operate the three technical Cores comprised of state-of-the-art flow cytometry, signal transduction, and Luminex technology, which will facilitate rapid analysis of host response gene products resulting from infection. The Projects of currently selected faculty were based on scientific merit, review by External Advisory Committee members, with a focus for complementary interaction with other Projects, potential for development into new research programs headed by senior faculty, and likelihood for receiving NIH grant support. Two of the technical Cores will be directed by two faculty members who were previously supported by the COBRE and who have each secured two NIH grants. The new program was developed in response to the new RFA that suggested recruitment of senior faculty who could help develop and head new research programs. One such senior faculty has already been recruited. Finally, the new program has been based on our track record in which eleven investigators supported by the previous COBRE have secured a total of 16 extramural grants. Eight of the eleven have secured 12 NIH grants.